1. Overview of Screening Visit Procedures, PTID Assignment, Screening & Enrolment Logs, and Screen Failures
Objectives:
Review screening visit procedures
Inclusion & Exclusion criteria
Discuss PTID assignment
Review Screening & Enrolment logs
Review dealing with screening failures

2. To keep in mind during screening & enrollment
What do we want to learn from HOPE?
When offered the ring as a CHOICE, will women use it with high adherence and safety, and achieve HIV protection?
How acceptable and feasible is the delivery of the microbicide vaginal ring?
CHOICE in HOPE means enrolment will be different.
How do these key goals impact what we are looking for in screening & enrolment?

3. Components of Screening Visit Slide 1
Questionnaires:
Demographics
Screening Behavioral Eligibility
Administrative:
Screening IC
Assign PTID
Assess eligibility
Locator
Schedule Next Visit*
Reimbursement
Behavioral:
HIV pre- & post-test
HIV/STI risk reduction (offer condoms)
Contraceptive counseling
You can find this in Table 5 (Screening Visit) of your protocol, on page 54.
Administrative: IC for SCR must be obtained prior to completion of any screening procedures. After consenting, ppts will be assigned a PTID and undergo a series of behavioral assessments, clinical evaluations, and laboratory tests. Location info will be collected initially during the screening visit, and updated at visits throughout the study. Staff must confirm adequate locator information is provided prior to enrollment as defined in your site SOP for retention.
Behavioral: Ppts receive HIV pre- & post- test counselling and risk reduction counseling including provision of condoms in conjunction with HIV testing during screening. Counseling considerations for screening and other visits will be reviewed in a separate and ongoing training and are described in Section 12 of the SSP.
Questionnaires: We recommend you complete these early in the screening visit so that the more time-consuming clinical and lab evals can be avoided if the ppt is ineligible due to behavioral criteria. We will cover the behavioral eligibility CRF later in this presentation. Demographics CRF administration (as well as other screening CRFs will be reviewed by SCHARP later on in the training).

4. Components of Screening Visit Slide 2
Clinical:
Medical/Menstrual Hx
Concomitant Meds
Contraceptive provision*
Physical Exam
Pelvic Exam
Treatment or referral*
Laboratory:
Urine:
Pregnancy
GC/CT
Urine culture*†
Pelvic:
Trichomonas
Pap Smear*
Laboratory:
Blood:
HIV Serology
CBC with platelets
Serum Chemistries
Syphilis Serology
You can find this in Table 4 (Screening Visit) of your protocol, on page 54.
Clinical: Clinical screening visit procedures are similar, but not as numerous, as for ASPIRE,. They are outlined in detail in Section 10 of the SSP, but generally:
clinical procedures include collection of medical, menstrual, pregnancy, and contraceptive history, con meds, contraceptive use, physical exam, and pelvic exam.
ppts will be evaluated for use of prohibited meds, STI/TRI/UTI, genital signs and symptoms, and overall general health
PAP smears are only needed for participants who do not have a documented normal result within the preceding 12 months
Lab: Details re lab tests and sample collection at screening will be discussed in detail later, and are in Section 13 of the SSP, but generally:
Ppts receive testing for syphilis, trich, and HIV, preg testing, serum chemistries, CBC with platelets.
If indicated, ppts may be tested and treated for BV, candidiasis, or herpes, per local std of care.
If indicated, a pap smear specimen will be collected.
As recommended on the previous slide, you might want to consider conducting quicker assessments first – and avoid doing pelvics on ppts who may not be eligible behaviourally, or in some other aspect. Prioritize your clinic flow to weed out ineligible folks early to use staff resources well.

5. Screening Window 56 Days There is no limit to screening attempts
Enrollment
56 Days
The term “screening attempt” is used to describe each time a participant screens for the study (i.e., each time she provides written informed consent for screening).
If all screening and enrollment procedures are not completed within 56 days of obtaining written informed consent for screening, the participant must repeat the entire screening process except for PTID assignment, beginning with the screening informed consent process.
If needed, screening visit procedures can be completed over multiple visits.
There is no limit to screening attempts

6. Screening Visit Checklist
Of note in the HOPE screening process, and shown here in the checklist, is the prescreening ID. If the participant is about to begin the screening process but does not yet have a prescreening ID, complete the prescreening ID process for her. The Pre-screening ID will be generated in Medidata.
Instructions: Complete staff initials next to procedures completed. Do not initial for other staff members. If other staff members are not available to initial checklist items themselves, initial and date a note on the checklist documenting who completed the procedure, e.g., “done by {name}” or “done by nurse.” If a procedure listed on the checklist is not performed, enter “ND” for “not done” or “NA” for “not applicable” beside the item and record the reason why (if not self-explanatory); initial and date this entry. If any procedures are not conducted on the date recorded above, ensure the date procedure conducted is included in the comments section. Use a new Screening Visit Checklist if a second screening attempt is needed.
The sequence of procedures presented on the visit checklists is a suggested ordering only. For screening, the only requirement is that IC be conducted before any per protocol procedures—other ordering is flexible.
This can be source for some procedures, but most procedures require additional documentation elsewhere. Refer to your source doc SOP document; this checklist is a tool for ensuring all the processes documented elsewhere are completed appropriately so staff has a snapshot of what needs to be done/resolved to complete eligibility assessments.

7. Screening Informed Consent
No per-protocol procedures can occur before screening IC is obtained (only pre-screening can happen prior to screening IC).
Who will be conducting screening IC at your site?
Note that the IC coversheet is a tool that helps capture all the required elements of documentation for IC. Use of this coversheet is strongly recommended. If used, one coversheet per IC would be completed (i.e. Screening, Enrollment, Storage)
IC comprehension survey isn’t required for screening--only at enrollment but sites could create a site-specific form if they wanted to administer a questionnaire at screening. 7

8. MTN-025/HOPE Inclusion Criteria
Previously enrolled in MTN-020 (ASPIRE)
Able and willing to provide written informed consent
Able and willing to provide adequate locator information
HIV-uninfected
Using an effective method of contraception at Enrollment, and intending to use an effective method for the duration of study participation. Effective methods include hormonal methods (except contraceptive ring); intrauterine contraceptive device (IUCD); and sterilization (of participant, as defined in site SOPs)
Agrees not to participate in other research studies involving drugs, medical devices, vaginal products, or vaccines for the duration of study participation
A clear difference in the inclusion criteria for HOPE is that all participants must have also participated in ASPIRE. This may change in the future, but for now only ASPIRE participants can participate in HOPE.
Participant sexual activity is no longer a factor in enrollment – provided they are former ASPIRE participants.

9. MTN-025/HOPE Exclusion Criteria
Study product use permanently discontinued in response to an AE or safety related concern while taking part in the MTN-020 (ASPIRE) trial
Per participant report at Screening:
Plans to relocate away from the study site during study participation
Plans to travel away from the study site for more than three consecutive months during study participation
Per participant report at Enrollment, currently taking Post-Exposure Prophylaxis (PEP)
PEP use at Screening is not exclusionary. Participants may be enrolled after the PEP regimen is complete and a negative HIV test is documented within 56 days of providing informed consent for Screening.
With the exception of MTN-020 (ASPIRE), participation in any other research study involving drugs, medical devices, vaginal products, or vaccines, within 60 days of enrollment
Participation in the ‘Decliner Population’ does not preclude MTN-025 full study participation in the future.
Variations from ASPIRE exclusion criteria:
Permanent product use discontinuation in ASPIRE
PEP use does not have to be 6 months in the past – as long as the regimen is completed and there is a negative HIV test, the participant can enroll
No PrEP study exclusion criteria

10. MTN-025/HOPE Exclusion Criteria
Is pregnant at Screening/Enrollment or planning to become pregnant in the participant’s anticipated study participation period
Is currently breastfeeding
Diagnosed with urinary tract infection (UTI), pelvic inflammatory disease (PID), STI or reproductive tract infection (RTI) requiring treatment per WHO guidelines
Note: Otherwise eligible participants may be enrolled after completing treatment if all symptoms have resolved.
Clinically apparent Grade 3 pelvic exam finding
Variations from ASPIRE exclusion criteria:
Pelvic finding is now Grade 3, not grade 2

11. MTN-025/HOPE Exclusion Criteria
Has any of the following laboratory abnormalities at Screening Visit:
Aspartate aminotransferase (AST) or alanine transaminase (ALT) > Grade 3
Creatinine > Grade 3
Hemoglobin > Grade 3
Platelet count > Grade 3
Pap result ≥ Grade 3
Has any significant medical condition or other condition that, in the opinion of the IoR/designee, would preclude informed consent, make study participation unsafe, complicate interpretation of study outcome data, or otherwise interfere with achieving the study objectives
Variations from ASPIRE exclusion criteria:
AST/ALT grade is 3, not 1
Creatinine, hemoglobin, platelet and pap results are grade 3, not 2
No specific exclusion criteria based on other medical conditions – however, this was rolled into the exclusion based on IoR discretion. these just must be documented in screening and enrollment logs as they are relevant.
No exclusion criteria based on recent genital/gynecological procedures
Also note: If the clinician feels that the participant is breastfeeding but not disclosing this information, the IoR can defer her enrollment under this tenth criteria item. Please reinforce/encourage breastfeeding as a healthy behavior.

12. Questions to evaluate behavioral eligibility criteria
Questions to evaluate behavioral eligibility criteria. Available in English and local languages. Serves as source documentation for these criteria.

13. Questions on Screening procedures?

14. PTID Name Linkage Log
Through Medidata, SCHARP will provide information on the generation of PTIDs for participants. Do not complete the PTID name linkage log until the screening informed consent is signed by the participant. Ppts keep the same PTID even if undergoing more than one screening attempt.
The act of associating a name with the PTID is considered “PTID assignment”. All participants will get a prescreening ID prior to IC; names should not be associated with this ID until after screening IC.
PTID Name Linkage Logs always are stored in a double-locked area to protect ppt confidentiality and should be kept separate from ppt binders
Use only 1 PTID per participant, regardless of screening attempt; unlimited screening attempts are allowed.
Note that a single PTID Name Linkage Log will be used for HOPE enrolled and decliner populations. Participants who have previously enrolled in the Decliner Group will retain the same HOPE PTID.
Discussion Question: who will be responsible for completing this log at your site?
[if there is time in this presentation, could raise talking point : During an early assessment visit, FHI 360 finds that one participant had a second screening attempt and was assigned two different PTIDs. Explain how this will be avoided at your site, including the specific tools and flow of procedures.]

15. Enrollment Screening Screen Fail
DAIDS policy requires Scr & Enr logs be maintained for every prospective ppt screened. This can be an electronic log (as long as none of the required elements are sourced here), or documented in hardcopy. These need to be used in real time and completed as soon as a prospect completes Scr IC (if a woman does not provide Scr IC, she should NOT be listed on this log). We may ask for these logs periodically to help with data cleaning.
Note on the log the column asking for Reason for screening failure/discontinuation- you’ll want to list ALL reasons she fails screening, if there is more than one reason.
What do you imagine happens for a ppt who is rescreened?
She is assigned a new row on the scr/enr log, number
Eligibility Criteria CRF would be updated for subsequent screening attempts.

16. Documentation for Screen Failures
Screening IC forms (IC/coversheet).
Document reasons for ineligibility and date of determination as per the Eligibility Checklist
ECI-1 and pre-screening CRF only – complete and enter into Medidata
Document necessary referrals in ppt’s file; document that clinically significant abnormalities were communicated to ppt (Ex. Grade 3 lab value)
Make sure all screening documentation is complete up until the time that ineligibility was determined, including screening visit Checklist
File or enter data for all documents per MTN Data Management SOP
In addition, the Screening and Enrollment Log should be updated with date of discontinuation of screening and reason for screen failure (list item number as appropriate from the Eligibility Checklist).

17. Screening Pop Quiz
Get out your quiz paper!

18. Screening Pop Quiz
If a participant screens out of HOPE, can she participate in the HOPE decliner group?

19. Screening Pop Quiz
How many screening attempts can be made for each participant?

20. Screening Pop Quiz
Name one difference between the eligibility criteria for HOPE and ASPIRE.

21. Screening Pop Quiz
Where does the pre-screening ID come from?

22. Screening Pop Quiz
How many days long is the screening window?

23. Screening Pop Quiz How did you do?
NO - Only participants who actively decline study participation (i.e., express disinterest in enrollment) should be considered for decliner group enrollment.
Trick question! No limit.
Variable
Medidata!
56 days long
1 - For example, if a participant was ineligible due to positive HIV or pregnancy testing she should not be considered for decliner population enrollment.
2 – No limit
3 – Ask for ideas and check back on other slides
4 – Prescreening ID comes from Medidata/SCHARP
5 – Screening window is 56 days long

24. Screening Visit References
Eligibility criteria protocol Sections 5.2/ 5.3
Screening procedures protocol Section 7.2; SSP Section 4
Visit Checklist Templates MTN Website 24

25. ANY further questions?